VEGF165 gene therapy (angiogenic plasmid)

This mechanism is a gene therapy approach: a plasmid, a small circular loop of DNA, encodes the VEGF165 isoform, a specific splice variant of vascular endothelial growth factor (VEGF). The therapeutic rationale is angiogenesis induction, the formation of new blood vessels, in tissue that has lost adequate blood supply. When the plasmid is delivered locally (typically by intramuscular injection), muscle cells take it up and transiently produce VEGF165 protein, which is secreted and binds to VEGF receptors on nearby endothelial cells, the cells lining blood vessels. This drives proliferation, migration, and organization of endothelial cells into new capillary networks and collateral vessels that can bypass blocked or narrowed arteries. The broad disease context is ischemic vascular disease, particularly peripheral arterial disease and critical limb ischemia, where restricted blood flow to the limbs causes pain, poor wound healing, and risk of tissue loss. Unlike protein or antibody therapeutics, a plasmid approach uses the patient's own cellular machinery as a temporary factory for the growth factor, avoiding repeated dosing of a manufactured protein. Because plasmid DNA generally does not integrate into the host genome and its expression is transient, the induced angiogenic stimulus is time-limited, which shapes both the potential benefit and the duration of any effect.